Cell culture and fermentation have value for many aspects of industrial production, such as pharmaceuticals, industrial enzyme production (e.g. detergents, food additives, textile processing, pulp and paper processing, grain processing incl. production of high fructose corn syrup), potable and fuel ethanol, amino acids, vitamins, feed additives, and many others. The actual organisms in the fermenter may vary greatly and can include a variety of bacteria, yeast, fungi, insect cells, mammalian cells, and others.
Conventionally, complex large-scale fermentation (hundreds of thousands of liters) systems are used for production. Large scale systems are manufactured by companies, such as Applikon, B. Braun, and New Brunswick Scientific. Typically, large scale cell culture and fermentation systems must be capable of: 1) feeding the media with nutrients, 2) measuring and changing the Oxygen level, 3) measuring and changing the temperature, 4) measuring and changing the pH level, 4) stirring the contents, 5) purging byproducts (such as CO2), and 6) monitoring the reaction quality (such as cell density and protein expression).
Before scaling up reactions in large capacity fermenters, similar reactions are typically performed at a smaller scale. Small-scale fermenters, e.g., in the 1-20 liter range, provide most if not all of the desired performance functions of the large scale fermenters described above. However, the small-scale fermenters are expensive, and have a relatively larger form than necessary for many desired applications.
For fermentations on a smaller scale, less expensive systems are used. Small-scale bioreactors (“microreactors”) are a tool of growing value to the microbiology community. They are used for screening of new strains, optimization of culture conditions, and for micro-scale production.
Due to the sensitivity of the reactions and measurements performed in microreactors, it is necessary to carefully control the environment in the wells of the microreactor. Accordingly, improvements on the control of the environment of the microreactors are desirable.